Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Does Intraspecific Size Variation in a Predator Affect Its Diet Diversity and Top-Down Control of Prey?

It has long been known that intraspecific variation impacts evolutionary processes, but only recently have its potential ecological effects received much attention. Theoretical models predict that genetic or phenotypic variance within species can alter interspecific interactions, and experiments have shown that genotypic diversity in clonal species can impact a wide range of ecological processes. To extend these studies to quantitative trait variation within populations, we experimentally manipulated the variance in body size of threespine stickleback in enclosures in a natural lake environment. We found that body size of stickleback in the lake is correlated with prey size and (to a lesser extent) composition, and that stickleback can exert top-down control on their benthic prey in enclosures. However, a six-fold contrast in body size variance had no effect on the degree of diet variation among individuals, or on the abundance or composition of benthic or pelagic prey. Interestingly, post-hoc analyses revealed suggestive correlations between the degree of diet variation and the strength of top-down control by stickleback. Our negative results indicate that, unless the correlation between morphology and diet is very strong, ecological variation among individuals may be largely decoupled from morphological variance. Consequently we should be cautious in our interpretation both of theoretical models that assume perfect correlations between morphology and diet, and of empirical studies that use morphological variation as a proxy for resource use diversity

Cryo Electron Tomography of Herpes Simplex Virus during Axonal Transport and Secondary Envelopment in Primary Neurons

During herpes simplex virus 1 (HSV1) egress in neurons, viral particles travel from the neuronal cell body along the axon towards the synapse. Whether HSV1 particles are transported as enveloped virions as proposed by the ‘married’ model or as non-enveloped capsids suggested by the ‘separate’ model is controversial. Specific viral proteins may form a recruitment platform for microtubule motors that catalyze such transport. However, their subviral location has remained elusive. Here we established a system to analyze herpesvirus egress by cryo electron tomography. At 16 h post infection, we observed intra-axonal transport of progeny HSV1 viral particles in dissociated hippocampal neurons by live-cell fluorescence microscopy. Cryo electron tomography of frozen-hydrated neurons revealed that most egressing capsids were transported independently of the viral envelope. Unexpectedly, we found not only DNA-containing capsids (cytosolic C-capsids), but also capsids lacking DNA (cytosolic A-/B-capsids) in mid-axon regions. Subvolume averaging revealed lower amounts of tegument on cytosolic A-/B-capsids than on C-capsids. Nevertheless, all capsid types underwent active axonal transport. Therefore, even few tegument proteins on the capsid vertices seemed to suffice for transport. Secondary envelopment of capsids was observed at axon terminals. On their luminal face, the enveloping vesicles were studded with typical glycoprotein-like spikes. Furthermore, we noted an accretion of tegument density at the concave cytosolic face of the vesicle membrane in close proximity to the capsids. Three-dimensional analysis revealed that these assembly sites lacked cytoskeletal elements, but that filamentous actin surrounded them and formed an assembly compartment. Our data support the ‘separate model’ for HSV1 egress, i.e. progeny herpes viruses being transported along axons as subassemblies and not as complete virions within transport vesicles

HDNetDB: A Molecular Interaction Database for Network-Oriented Investigations into Huntington’s Disease

Huntington's disease (HD) is a progressive and fatal neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin gene. Although HD is monogenic, its molecular manifestation appears highly complex and involves multiple cellular processes. The recent application of high throughput platforms such as microarrays and mass-spectrometry has indicated multiple pathogenic routes. The massive data generated by these techniques together with the complexity of the pathogenesis, however, pose considerable challenges to researchers. Network-based methods can provide valuable tools to consolidate newly generated data with existing knowledge, and to decipher the interwoven molecular mechanisms underlying HD. To facilitate research on HD in a network-oriented manner, we have developed HDNetDB, a database that integrates molecular interactions with many HD-relevant datasets. It allows users to obtain, visualize and prioritize molecular interaction networks using HD-relevant gene expression, phenotypic and other types of data obtained from human samples or model organisms. We illustrated several HDNetDB functionalities through a case study and identified proteins that constitute potential cross-talk between HD and the unfolded protein response (UPR). HDNetDB is publicly accessible at http://hdnetdb.sysbiolab.eu.CHDI Foundation [A-2666]; Portuguese Fundacao para a Ciencia e a Tecnologia [SFRH/BPD/70718/2010, SFRH/BPD/96890/2013, IF/00881/2013, UID/BIM/04773/2013 - CBMR, UID/Multi/04326/2013 - CCMAR]info:eu-repo/semantics/publishedVersio

Neoproterozoic glaciomarine and cap dolostone facies of the southwestern Taoudeni Basin (Walidiala Valley, Senegal/Guinea, NW Africa)

The Neoproterozoic-age Mali Group of the southwestern Taoudéni Basin, NW Africa, represents, in the Walidiala Valley, a glaciogenic and post-glacial succession that brackets the Cryogenian-Ediacaran period boundary. At its base, debris flows and turbidite-like, sandy units of the Pelel Member pass upward into siltstone and shale of the Diagoma Member. These two units represent the progressive evolution from some portion of a fan delta fed by a nearby ice shelf to a more distal environment disturbed only by the occasional fallout from passing icebergs. The appearance of coarse-grained, cross-bedded sandstone beds and gravels of the overlying Tanagué Member heralds a return to a shallower, fluvially influenced environment before abrupt transgression caps the glaciogenic succession. The transgressive unit consists of a regionally extensive, 2-7 m-thick, silty dolostone, the Bowal Member, which is isotopically and petrographically indistinguishable from ca. 635-Ma cap dolostone units elsewhere in NW Africa and worldwide. The Bowal Member comprises microcrystalline dolomite in turbidite-like depositional sheets disrupted by internal brecciation, fracturing and cementation by first chert and then dolomite. The stratigraphic succession in the Walidiala Valley closely resembles facies models relating to glacial retreat in a proximal glaciomarine environment affected by glacioeustasy. A large volcaniclastic debris flow has caused slumping and soft-sediment deformation within the cap dolostone of the Bowal Member. The widespread association of pyroclastic deposits with cap dolostone throughout the Taoudéni Basin implies that volcanism and deglaciation were roughly contemporaneous across a huge area. We consider that the volcaniclastic debris flow and soft-sediment deformation within the underlying Tanagué Member were possibly triggered by seismic activity during deglaciation, caused by isostatic relaxation of the lithosphere. However, fitted brecciation of cap dolostone beds here and elsewhere in the world is more consistent with pervasive dolomite cementation. © 2006 Académie des sciences

Reconstructing Holocene sea-level change for the central Great Barrier Reef using subtidal foraminifera

We assessed the utility of subtidal foraminifera to reconstruct Holocene relative sea levels from the central Great Barrier Reef shelf, Australia. We collected contemporary foraminiferal samples from Cleveland Bay and Bowling Green Bay, with water depths from -4.2 in to -48.0 m Australian Height Datum (AHD). The subtidal foraminiferal assemblages were divided into two distinct foraminiferal zones: an inner shelf zone occupied by Elphidium hispidulum, Pararotalia venusta, Planispirinella exigua, Quinqueloculina venusta and Triloculina oblonga; and a middle shelf zone dominated by Amphistegina lessonii, Dendritina striata and Operculina complanata. The zonations of the study areas and relative abundances of individual species indicate that the distributions of subtidal foraminifera are related to water depth. We used the subtidal data to develop a transfer function capable of inferring past water depths of sediment samples from their foraminiferal content. The results indicated a robust performance of the transfer function (r(2)jack = 0.90). We produced ten sea-level index points, which revealed an upward trend of Holocene relative sea level from -8.86 +/- 4.5 m AHD at 9.3-8.6 cal kyr BP to a mid-Holocene high stand of +1.72 +/- 3.9 m AHD at 6.9-6.4 cal kyr BP. Sea level subsequently fell from the highstand to the present-day. The sea-level reconstructions are consistent with geophysical models and previous published data